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Photoreaction Between Benzoylthiophenes and N ‐BOC‐Tryptophan Methyl Ester ‡
Author(s) -
PérezPrieto Julia,
MorantMiñana Maria C.,
Galian Raquel E.,
Miranda Miguel A.
Publication year - 2006
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/2005-03-15-ra-461
Subject(s) - chemistry , ketyl , radical , hydrogen atom abstraction , isopropyl , aryl , tryptophan , context (archaeology) , ketone , photodissociation , flash photolysis , stereochemistry , medicinal chemistry , photochemistry , amino acid , organic chemistry , kinetics , quantum mechanics , reaction rate constant , biology , paleontology , biochemistry , alkyl , physics
Drug‐induced photoallergy requires as the first step formation of covalent drug‐protein photoadducts. One of the key amino acids involved in this process is tryptophan (Trp). In this context, several diaryl ketones, including 2‐benzoylthiophene (BT), [2‐(5‐benzoyl‐5‐thienyl)]‐2‐methylpropanoic methyl ester (TPA methyl ester) and 4‐(2‐thienylcarbonyl)phenyl]‐2‐methylpropanoic methyl ester (SUP methyl ester) have been irradiated in the presence of N ‐BOC‐( L )‐tryptophan methyl ester. Laser flash photolysis has allowed to detect three neutral radicals (ketyl, indolyl and skatolyl radicals) resulting from formal hydrogen‐atom abstraction. This correlates well with the isolation of homodimers, as well as with cross‐coupling products, in the preparative irradiation. The main cross‐coupling products were in all cases lactones arising from the reaction of the Trp‐derived skatolyl radicals with the corresponding ketyl radicals. These lactones were obtained as the (4 R ) stereoisomers with remarkable diasteroselectivity. No coupling products through the phenyl p ‐position of BT or TPA methyl ester were found. By contrast, ketone homodimers and cross‐coupling products arising from reaction through the thienyl 5‐position were obtained when using BT and SUP methyl ester; this is very interesting, because stable LAT‐derived products are difficult to isolate.